Polymer-drug conjugates as inhalable drug delivery systems: A review

Accelerating interest by the pharmaceutical industry in the identification and development of less invasive routes of nanomedicine administration, coupled with defined efforts to improve the treatment of respiratory diseases through inhaled drug administration has fuelled growing interests in inhalable polymer-drug conjugates. Polymer-drug conjugates can alter the pharmacokinetic profile of the loaded drug after inhaled administration and enable the controlled and sustained exposure of the lungs to drugs when compared to the inhaled or oral administration of the drug alone. However, the major concern with the use of inhalable polymer-drug conjugates is their biocompatibility and long-term safety in the lungs, which is closely linked to lung retention times. A detailed understanding about the pharmacokinetics, lung disposition, clearance and safety of inhaled polymer-drug conjugates with significant translational potential is therefore required. This review therefore provides a comprehensive summary of the latest developments for several types of polymer-drug conjugates that are currently being explored as inhalable drug delivery systems. Finally, the current status and future perspective of the polymer-drug conjugates is also discussed with a focus on current knowledge gaps

Study on Oral Hygiene Practices, Tobacco use, and Food Habits among Tharu Community of Gadi Rural Municipality, Nepal

Background An unhealthy diet with high sugar content use of tobacco high consumption of alcohol and poor oral hygiene are common factors affecting the oral health of people This study was conducted to explore oral hygiene practices use of tobacco and food habits among Tharu people the indigenous community in the Gadi rural municipality of Sunsari Nepal Methods A community-based cross-sectional study was conducted at the Tharu community of Gadi rural municipality Sunsari Nepal from February to August 2015 using a purposive sampling method A face-to-face interview was used to collect data Descriptive statistics were performed using the IBM-SPSS 17 0 Results Females were predominant 57 9 in this study About 86 8 of the participants used a toothbrush with toothpaste as a method of cleaning their teeth 81 76 brushed once a day 84 3 brushed in the morning Almost 80 of the participants brushed their teeth using fluoridated toothpaste The majority 75 of the participants replied that they change their toothbrush for at least 6 month

Bioequivalence study of two brands of phenytoin sodium 100mg formulations in healthy adult male rabbits

The objective of the study was to compare the bioavailability of a single oral 100 mg dose of two brands of phenytoin sodium formulations available in the Nepalese market. Formulation B was taken as test drug and compared with the innovator brand which was taken as reference standard. A randomized, two-way crossover study was done in six healthy adult male rabbits. All six rabbits received a single oral 100 mg dose of both the formulations with a two-week washout period between the formulations. Blood samples for plasma phenytoin levels were collected at 0.25, 1, 2, 4, 6, 8, 10, 12, 16, 24 hours. The pharmacokinetic parameters of the two brands of phenytoin sodium calculated were area under the concentration versus time curve from time zero to 24 hours (AUC 0-24), Area under the Curve from time zero to infinity (AUC(0-infinity)), peak plasma concentration (C-max) and time of peak concentration (t(max)). Formulation B failed to comply in terms of Area under the Curve (AUC), an important pharmacokinetic parameter to test bioequivalency, which was tested at significance level 0.05. This showed that the test formulation is not bioequivalent with the innovator. Taken together, our preliminary findings suggest that further studies in a large population is needed before switching phenytoin brands once a patient is carefully titrated to a given phenytoin brand

Lipid core peptide/poly(lactic-co-glycolic acid) as a highly potent intranasal vaccine delivery system against Group A streptococcus

Rheumatic heart disease represents a leading cause of mortality caused by Group A Streptococcus (GAS) infections transmitted through the respiratory route. Although GAS infections can be treated with antibiotics these are often inadequate. An efficacious GAS vaccine holds more promise, with intranasal vaccination especially attractive, as it mimics the natural route of infections and should be able to induce mucosal IgA and systemic IgG immunity. Nanoparticles were prepared by either encapsulating or coating lipopeptide-based vaccine candidate (LCP-1) on the surface of poly(lactic-co-glycolic acid) (PLGA). In vitro study showed that encapsulation of LCP-1 vaccine into nanoparticles improved uptake and maturations of antigen-presenting cells. The immunogenicity of lipopeptide incorporated PLGA-based nanoparticles was compared with peptides co-administered with mucosal adjuvant cholera toxin B in mice upon intranasal administration. Higher levels of J14-specific salivary mucosal IgA and systemic antibody IgG titres were observed for groups immunized with encapsulated LCP-1 compared to LCP-1 coated nanoparticles or free LCP-1. Systemic antibodies obtained from LCP-1 encapsulated PLGA NPs inhibited the growth of bacteria in six different GAS strains. Our results show that PLGA-based lipopeptide delivery is a promising approach for rational design of a simple, effective and patient friendly intranasal GAS vaccine resulting in mucosal IgA response

Subunit-based mucosal vaccine delivery systems for pulmonary delivery - Are they feasible?

Pulmonary infections are the most common cause of death globally. However, the development of mucosal vaccines that provide protective immunity against respiratory pathogens are limited. In contrast to needle-based vaccines, efficient vaccines that are delivered via noninvasive mucosal routes (such as via the lungs and nasal passage) produce both antigen-specific local mucosal IgA and systemic IgG protective antibodies. One major challenge in the development of pulmonary vaccines using subunit antigens however, is the production of optimal immune responses. Subunit vaccines therefore rely upon use of adjuvants to potentiate immune responses. While the lack of suitable mucosal adjuvants has hindered progress in the development of efficient pulmonary vaccines, particle-based systems can provide an alternative approach for the safe and efficient delivery of subunit vaccines. In particular, the rational engineering of particulate vaccines with optimal physicochemical characteristics can produce long-term protective immunity. These protect antigens against enzymatic degradation, target antigen presenting cells and initiate optimal humoral and cellular immunity. This review will discuss our current understanding of pulmonary immunology and developments in fabricating particle characteristics that may evoke potent and durable pulmonary immunity

Oral delivery of nanoparticle-based vaccines

Most infectious diseases are caused by pathogenic infiltrations from the mucosal tract. Therefore, vaccines delivered to the mucosal tissues can mimic natural infections and provide protection at the first site of infection. Thus, mucosal, especially, oral delivery is becoming the most preferred mode of vaccination. However, oral vaccines have to overcome several barriers such as the extremely low pH of the stomach, the presence of proteolytic enzymes and bile salts as well as low permeability in the intestine. Several formulations based on nanoparticle strategies are currently being explored to prepare stable oral vaccine formulations. This review briefly discusses several molecular mechanisms involved in intestinal immune cell activation and various aspects of oral nanoparticle-based vaccine design that should be considered for improved mucosal and systemic immune responses

Intranasal delivery of nanoparticle-based vaccines

Most pathogens gain access to the human body and initiate systemic infections through mucosal sites. A large number of currently marketed licensed vaccines are parenterally administered; they generate strong systemic immunity but not mucosal immunity. Nasal vaccination is an appealing strategy for the induction of mucosal-specific immunity; however, its development is mostly challenged by several factors, such as inefficient antigen uptake, its rapid mucociliary clearance, size-restricted permeation across epithelial barriers and absence of safe human mucosal adjuvants. Therefore, a safer mucosal-adjuvanting strategy or efficient mucosal delivery platform is much warranted. This review summarizes challenges and the rationale for nasal vaccine development with a special focus on the use of nanoparticles based on polymers and lipids for mucosal vaccine delivery

Use of Antidepressants among Patients Diagnosed with Depression: A Scoping Review

Introduction. Depression is a major global health problem with a relatively high lifetime prevalence and significant disability. Antidepressants are the most effective medications used for the treatment of depression. Hence, this study is aimed at summarizing the studies on antidepressant use among patients diagnosed with depression. Method. PubMed, Embase, Web of Science, Scopus, and Google Scholar were searched for literature (2000-2019) using keywords such as depression, drug utilization, antidepressants, prescription, serotonin reuptake inhibitor, serotonin and norepinephrine reuptake inhibitor, tricyclic antidepressants, and atypical antidepressants. Results. Antidepressant users were mostly females, married people, housewives, lower-income people, employees, and highly educated people, as they were found to be more prone to develop depression than their counterparts. Selective serotonin reuptake inhibitors (SSRIs), such as sertraline, were most commonly prescribed among depressive patients. Conclusion. Our study suggested that out of five major antidepressant drugs available for the treatment of depression, selective serotonin reuptake inhibitors are preferred over others because of their better side effects and tolerability profile